Infiltrating Lobular Carcinoma Research Articles

Recurrence in lobular carcinoma of the breast: A 14-year review.

The two most common types of breast cancer are invasive or infiltrating ductal carcinoma (IDC) and invasive or infiltrating lobular carcinoma (ILC) (Pestalozzi etal., J. Clin. Oncol., 26, 2008, 3006). Between 5% and 15% of invasive breast carcinomas are lobular carcinomas (Pestalozzi etal., J. Clin. Oncol., 26, 2008, 3006; Dossus and Benusiglio, Breast Cancer Res., 17, 2015, 37; Braunstein etal., Breast Cancer Res. Treat., 149, 2015, 555). The paucity of data relating to recurrence rates of lobular cancers prompted this study. A retrospective cohort study of all cases of lobular breast carcinoma reported to the Western Australia Cancer Registry with the clinical and pathological details between 2000 and 2014. Overall, 2463 subjects with a total of 2526 events of invasive lobular carcinoma of the breast. 11/2463 (0.45%) subjects met criteria for local recurrence of invasive lobular breast cancer, with an incidence of 1 in 224. There are clinical implications for the management and follow-up for patients with a diagnosis of lobular cancer of the breast. Due to the low recurrence rate, now, the standard practice in our institution does not offer magnetic resonance imaging (MRI) as part of the follow-up for ILC patients. Other centres should establish local recurrence rates to aid development of appropriate management protocols.

Pushing the envelope in breast conserving surgery − is multiple-wire localization (3 or more wires) associated with increased risk of compromised margins and long-term recurrence?

IntroductionIn the last two decades there has been a paradigm shift with breast conserving surgery (BCS) being applied to larger and more extensive breast malignancies. The aim of this study is to examine the success of BCS being performed in patients with extensive breast malignancies requiring at least 3 wires for localization, and to assess possible risk factors for failure. Materials and methodsWe performed a retrospective single center review of 232 patients who underwent BCS between 2010 and 2020 requiring at least 3 wires for localization, thus comprising the multi-wire group (MWG). The cohort included a control group of 232 single-wire BCS patients (SWG) chronologically matched with the MWG. Patients with either invasive malignancy or ductal carcinoma in situ (DCIS) were included in the study. Clinical, radiological, and pathological data was collected. Proportions of positive surgical margins, re-lumpectomies and conversion to mastectomy were calculated. Survival analysis for locoregional and distant recurrence was performed. ResultsWomen in the MWG were younger (mean age 57 vs. 63.1, P < 0.001), had larger tumor size (mean size 5.1 cm vs. 1.3 cm, p < 0.001), a higher prevalence of calcifications on mammograms (72 % vs. 17 %, P < 0.001), a higher proportion of positive lymph nodes (75 % vs. 45 %, P = 0.019), and an elevated incidence of a ductal carcinoma in situ (DCIS) component (72 % vs. 38 %, P < 0.001).Positive surgical margins were higher in the MWG (13 % vs 7 %, P = 0.03), which lead to higher proportions of re-lumpectomies or conversion to mastectomies (7 % vs 4 %, P = 0.17). On multivariate analysis of the entire cohort, patients with positive margins were more likely to have a DCIS component (77 % vs 53 %, P = 0.001), an infiltrating lobular carcinoma (ILC) component (15 % vs 9 %, P = 0.013), and positive ER hormonal status (94 % vs 85 %, p = 0.05). The number of wires was not an independent predictor of positive margins.On long-term analysis, the locoregional disease-free survival was similar between the SWG and MWG (P = 0.1). However, the MWG showed higher rates of distant metastasis (12 % vs 4 %, P = 0.006). ConclusionsBCS requiring 3 or more wires is associated with a slightly higher proportion of positive margins. The increased risk of positive margins appears to be related to the type of tumor (DCIS component, ILC component and ER status) rather than to the number of wires. The number of wires does not significantly impact locoregional disease-free survival.

Metastatic profiles and survival differences between infiltrating ductal carcinoma and infiltrating lobular carcinoma in invasive breast cancer

BackgroundIn this study, we conducted a comprehensive evaluation of metastatic profiles and survival outcomes in patients with infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) treated at our university hospital center. MethodsWe collected and analyzed data from all patients diagnosed with invasive breast cancer at our center between January 1, 2007, and 31 December 2014. We specifically compared three subgroups: patients with IDC, patients with ILC and patients with mixed carcinoma, which is a combination of IDC and ILC. ResultsAmong the 1963 patients treated for invasive breast cancer in our center during the study period, 1435 had IDC, 466 had ILC, and 59 had mixed carcinoma. The incidence of patients with at least one positive axillary lymph node differed significantly: 40 % for IDC, 36 % for ILC, and 45 % for mixed carcinoma (p = 0.001). However, there was no significant difference in the mean number of positive nodes (p = 0.1633). The occurrence of distant metastases was lower in patients with ILC (p = 0.04), particularly in the case of brain metastases (p = 0.01), although there was no difference in bone or visceral metastatic sites. Patients with ILC exhibited a longer mean time to metastasis from the initial diagnosis of invasive breast carcinoma. Overall survival (p = 0.0525) and survival without locoregional recurrence (p = 0.026) were significantly different. Specifically, the 5-year overall survival rates for IDC, ILC, and mixed carcinoma were approximately 95 %. Distance metastatic-free survival at 5 years was 85 % for IDC, 91 % for ILC, and 87 % for mixed carcinoma (p = 0.00506). ConclusionOur findings indicate variations in the distribution of distant metastatic sites among patients with IDC, ILC, and mixed carcinoma, as well as differences in survival outcomes. This study sheds light on the unique characteristics and clinical implications associated with these two distinct subtypes of invasive breast cancer.

Evaluation of donut mastopexy as a conservative breast surgery in juxta areolar early breast cancer

Background In order to give a treatment as effective as mastectomy with the added benefit of a preserved breast, breast conserving surgery has evolved into the accepted course of action for the diagnosis and treatment of breast cancer. Donut mastopexy is one of the cancer breast surgery techniques that is used. Objective Evaluation of donut mastopexy as a conservative breast surgery in juxta areolar breast cancer. Methods A total of 50 female patients with early breast cancer near nipple-areolar complex were enrolled. Cosmetic outcome was evaluated during the early postoperative period and on follow-up. Operative time, intra and postoperative bleeding, drain content, wound complication as seroma or surgical site infection, symmetry, patient and doctor satisfaction were evaluated. Results Breast imaging reporting and data system (BI-RADS) classification of the obtained specimens of the study population showed that 12 (24%) had grade 4 and 38 (76%) had grade 5. Preoperative tru-cut biopsies of the obtained specimens of the study showed that 34 women (68%) had infiltrative ductal carcinoma, 10 women (20%) had ductal carcinoma in situ, four women (8%) had infiltrative lobular carcinoma and two women (4%) had mucinous carcinoma. Preoperative true-cut biopsies of the obtained specimens showed that 34 patients (68%) had infiltrative ductal carcinoma, 10 patients (20%) had ductal carcinoma in situ, four patients (8%) had infiltrative lobular carcinoma and two patients (4%) had mucinous carcinoma in-situ component of the obtained specimens showed that 13 patients (26%) had no in-situ component, 16 patients (32%) had less than or equal to 5% and 21 patients (42%) had greater than 5-25% intraoperative bleeding were three patients (6%); mean of drain content (volume) was 26.29±2.79 and mean of operative time (min) was 93.16±13.62. The most common complication was seroma (10%) and four patients (8%) were bleeding; followed by hematoma and delayed wound healing, and there was agreement on the ratio (6%) and infection and axillary wound seroma, and there was agreement on the ratio (4%), on the other hand partial nipple/skin necrosis and wound dehiscence was the lowest noticed complication, and there was agreement on the ratio (2%); as for the surgical site infection was five patients (10%) were hotness, four patients (8%) were redness and three patients (6%) were swelling. The patient satisfaction was 33 patients (66%) were excellent of satisfaction, nine patients (18%) were very good of satisfaction, seven patients (14%) were good satisfaction, and one case (2%) was poor satisfaction. Additionally, there was 31 doctors (62%) were excellent of satisfaction, 11 doctors (22%) were very good of satisfaction, 8 doctors (16%) were good satisfaction, while there is no poor cases among doctor satisfaction. Conclusion Donut mammography results in good cosmetic results. The study’s overall cosmetic outcome was more gratifying, and this was evident in the patients’ psychological health and sense of self-worth.

Abstract P6-04-05: A fully automatic artificial intelligence system for accurate and reproducible HER2 IHC scoring in breast cancer

Abstract Objective: Tumor HER2 expression is a key prognostic and treatment influencing factor in breast cancer. As with all immunohistochemistry (IHC) staining, visual interpretation of HER2 expression is subjective, which leads to intra- and inter-pathologist variability. Recent findings on the efficacy of HER2-targeted therapy on HER2-low patients raise the need for accurate and reproducible scoring. We developed a fully automated, artificial intelligence (AI) -based algorithm for HER2 scoring. The algorithm was based on ASCO/CAP 2018 guidelines and validated against rigorous ground truth (GT) established by multiple blinded expert pathologists. Methods: Algorithm development: We developed a solution that employs two steps: The first step consists of an ensemble of Deep Learning networks that process tissue regions and classify them as various tissue classes: Invasive cancer, Ductal Carcinoma In Situ (DCIS) and other morphologies. These networks were trained on slides that were automatically labeled by a separate AI system that analyzed the corresponding H&amp;E slides and projected its findings to the HER2 IHC slides using a registration algorithm. To further enrich the training set, especially with rare and difficult cases, a team of 8 expert pathologists manually marked tissue areas and assigned them to one of the tissue classes. In total, the training set consisted of 6,400 manual annotations and 1,300 automatically-annotated slides, both collected from 9 laboratories and scanned using 3 different scanners. The second step is an ensemble of Object Detection networks that process only the regions classified as invasive cancer, detect the tumor cells within them, and classify their staining pattern (e.g., Not stained, Moderate incomplete, etc.). Finally, the detected cells are counted, and the ASCO/CAP guidelines are applied to derive the slide-level HER2 score. Validation: The validation set was comprised of 453 HER2 slides stained using the VENTANA anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody as per manufacturer’s instructions. HER2 slides included biopsies and excisions with different breast cancer diagnoses (e.g., Infiltrating Ductal Carcinoma (IDC), Infiltrating Lobular Carcinoma (ILC), rare invasive subtypes, with and without DCIS) from 3 different laboratories. Ground truth was established by the consensus scores of a panel of 3 pathologists, who scored HER2 according to the guidelines without additional clinical considerations, such as scoring borderline 1+/2+ cases as 2+ to have additional tests performed. Results: The algorithm showed very high performance for detecting invasive cancer in HER2 tissue sections, with AUC of 0.967 (measured on 4-fold Cross-Validation classifying invasive vs. other regional classes). The algorithm demonstrated an overall accuracy of 80.3% for the HER2 scores when compared to the GT. When using different cutoffs for binary classification the resulting performance was: for 0 vs 1+/2+/3+ Kappa was 0.800; 0/1+ vs 2+/3+ Kappa was 0.728; for 0/1+/2+ vs 3+ Kappa was 0.954. The Quadratic Kappa between the AI score and the GT was 0.898, which is considered almost perfect. The performance of the AI was similar across the different laboratories and diagnoses(e.g. IDC, ILC). Conclusion: This study reports the successful development and independent validation of a fully automatic AI-based solution for accurate HER2 scoring in breast cancer. AI solutions, such as the one reported here, could be used as decision-support tools for pathologists in routine clinical practice, enhancing the reproducibility and consistency of HER2 scoring, thus enabling optimal treatment pathways and better patient outcomes. Accurate and automatic IHC scoring solutions can also contribute to the development of new prognostic, predictive and companion diagnostic tools. Citation Format: Yuval Globerson, Lilach Bien, Jonathan Harel, Giuseppe Mallel, Geraldine Sebag, Michel Vandenberghe, Craig Barker, Tsuyoshi Matsuo, Charo Garrido, Judith Sandbank, Chaim Linhart. A fully automatic artificial intelligence system for accurate and reproducible HER2 IHC scoring in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-04-05.

Metastatic Lobular Carcinoma of the Breast Masquerading as Gallstone Disease – A Case Report

The gallbladder is a rare site of breast cancer metastasis. We report the patient case of a 60-year-old woman with isolated metastasis to the gallbladder, which was surgically removed for symptomatic cholelithiasis, with a subsequent new diagnosis of infiltrating lobular carcinoma (ILC) of the breast. ILC tends to metastasize to unusual sites such as the gastrointestinal and genitourinary tracts, but these usually occur concurrently with other more common sites of distant metastasis such as the bone, lungs, and liver. Our case underscores the need for routine histologic examination of gallbladder after cholecystectomy.

Clinical Characteristics and Survival Outcomes of Infiltrating Lobular Carcinoma: A Retrospective Study of 365 Cases in China.

PurposeThe objective of this study was to compare the demographic characteristics, clinicopathological factors and survival outcomes between infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) using our single-center database.MethodsSeventeen thousand two hundred and three breast cancer patients were treated at Fudan University Shanghai Cancer Center (FUSCC) from January 2000 to December 2017. We identified 365 cases with ILC and 16,838 cases with IDC. The Pearson chi-square test was used to compare tumor characteristics, and the Kaplan–Meier methods were used to perform the survival analysis.ResultsILC had some distinctive characteristics from IDC such as older age (ranged from 61 to 80: ILC 26.8% vs IDC 19.9%, P < 0.001; over 80: ILC 1.6% vs IDC 0.8%, P < 0.001), larger tumor size (ranged from 2 to 5: ILC 45.2% vs IDC 37.1%, P = 0.011), much more hormone receptor expression (ILC 92.9% vs IDC 73.0%, P < 0.001), extremely less HER-2 expression (ILC 7.1% vs IDC 25.9%, P < 0.001). The overall survival and disease-free survival of ILC were worse than IDC (5-year OS, ILC 93.6% vs IDC 94.5%, P < 0.001; 5-year DFS, ILC 88.5% vs IDC 91.6%, P = 0.008). It was worth noting that the ILC patients had a worse overall survival than IDC patients after our propensity score matching study (P = 0.037). The univariate analysis concluded that positive HR (hormone receptor), high expression of Ki-67 and higher pathologic tumor stage were poor prognostic markers of ILC. Multivariate analysis demonstrated that tumor stage was a poor prognostic marker after adjustment for the effects of the above three factors. The most common primary site of metastasis was bone, but the proportion in the ILC group was much higher than that in the IDC group (56.25% vs 36.40%, P = 0.003).ConclusionCompared with IDC, ILC survived worse and was more prone to bone metastasis. Therefore, a comprehensive understanding of ILC and specific treatments are needed for further research.

Role of MicroRNA-31 (miR-31) in Breast Carcinoma Diagnosis and Prognosis.

Breast cancer (BC) is among the most widespread malignant tumors in women. In the current study, we evaluated the role of miR-31 in BC patients and its relation to the different prognostic, clinical, and pathological features. MiR-31 levels were determined by RT-PCR in BC and adjacent normal breast tissues from 100 BC patients. BC diagnosis was established through histopathological examinations. The expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) receptor in all tumors was determined using immunohistochemistry. MiR-31 expression was reduced in BC tissues relative to adjacent healthy breast tissue (mean levels were 0.93 and 7.2, respectively). Also, the low expression of miR-31 in BC patients was significantly correlated with adverse clinical and pathological features such as: young patient's age, premenopausal status, infiltrative lobular carcinoma, ER and PR negative tumors, HER2 positive tumors, and advanced clinical stage. MiR-31 was expressed at low levels in BC tissues and correlated with adverse clinical and pathological features, and poor survival.

ROLE OF SONOMAMMOGRAPHY IN MONITORING THE RESPONSE OF NEOADJUVANT CHEMOTHERAPY IN MALIGNANT BREAST MASSES

Abstract Background Breast cancer is a leading cause of death and disability between women, particularly young women, in low- and average -income countries (Porter, 2018). Neoadjuvant chemotherapy (NAC) is increasingly used in management patients with locally advanced breast cancer (LABC) (Mougalian et al., 2015). Mammography and breast ultrasound are the most widest diagnostic techniques used to evaluate primary tumor size and character at the time of diagnosis and monitoring the response to NAC (Kald et al., 2015). Aim of the work The purpose of this study is to assess and evaluate the role and the accuracy of Mammography and breast ultrasound modalities in monitoring the response of the breast cancer to the neoadjuvant chemotherapy. Patients and methods Twenty three patients presenting with pathologically proven malignant mass and conducted for neoadjuvant chemotherapy with age above 40 years-old. They were referred to the radiology department (mammography unit, Ultrasound unit and MRI unit) at El Salam oncology center, during the period between December 2018 to June 2019. Once a patient satisfied the inclusion and exclusion criteria for this study, an elaborate history was taken from all the patients which was followed by a thorough clinical evaluation, in which duration of symptoms, affected side, affected breast and family history. Patients were subjected to evaluation before starting neoadjunant chemotherapy by mammography, ultrasound and MRI as well as after finishing the neoadjuvant cycles which usually was ranging 3-4 cycles. Results Total of 23 patients with breast cancer were enrolled in this study. The patients were in the age group of 41-70 years with mean age of 54 years. Majority of patients had infiltrative ductal carcinoma IDC (16 cases -69.56% and the rest of cases were infiltrative lobular carcinoma (9 cases -39.13 %). After monitoring the response of the cases to neoadjuvant chemotherapy the results showed significant regressive course to the majority of cases ( 17 cases ) (73.91%) with the rest non respondent cases divided to cases with stationary ( 3 cases ) (13.04% ) and cases with progressive course ( 3 cases ) (13.04% ). The comparison between the results of Sonomammographic assessment of the breast lesions before and after the neoadjuvant chemotherapy cycles and also to MRI show close results. There were 5 cases that showed non-respondent (including stationary course and progressive course) in both Sonomammography and MRI and only one case that was respondent according to Sonomammography and non-respondent according to MRI breast (false +e). On the other hand there were 16 cases that had showed respondent fashion in both Sonomammography and MRI. Also there was one case that had showed non-respondent course according to Sonomammography and was respondent according to MRI results (false –ve). Sonomammography sensitivity was 94.12 % and specificity was 83.33% compared to MRI results, with high accuracy value reaching to 91.30 %. Conclusion The ability of mammography and breast ultrasound to accurately measure residual tumor size following neoadjuvant chemotherapy compared to Breast MRI measurement of the residual tumor demonstrated sensitivity of 94.12 % and specificity of 83.33% with high accuracy value reaching to 91.30 %. Even that the MRI is proved to be of high accuracy in detecting residual tumor, sonomammographic imaging isa cost-effective imaging modality than the MRI with sensitivity and specificity near to that of MRI.

Real-world clinical analysis and overall survival-related biomarker of breast cancer (BC) patients under 35 years old.

e12569 Background: Breast cancer (BC) is one of the most common malignant tumors among women in the world. Although under 7% of all BC cases, young BC is more difficult to diagnose and can be aggressive and less likely to respond to treatment. Exploring and identifying potential biomarkers for the diagnosis and prognosis of younger BC patients is necessary. Methods: A total of 1,202 BC patients under 35 years old (YD) were enrolled. Deep sequencing targeting 450 cancer genes was performed in a laboratory accredited by College of American Pathologists (CAP) and certified by Clinical Laboratory Improvement Amendments (CLIA) for genomic alteration identification. Statistical analysis was performed by Fisher’s exact test. Results: Of 1,202 young BC patients, 3 were under 20 YD, 85 were 20-25 YD, 371 were 26-30 YD, and 747 were 31-35 YD. Based on pathological, there were 899 infiltrative duct carcinomas, 10 infiltrative lobular carcinomas, and 292 BCs with unclear pathological type. According to molecular features, 587 HR+/HER2- (group I), 118 HR+/HER2+ (group II), 75 HR-/HER2+ (group III) and 193 HR-/HER2- (group IV) were included. Chemotherapy, radiotherapy, endocrine therapy and targeted therapy were received and 1074 patients were followed up. The median overall survival (OS) was 76 (5-156) months. There was no significant difference in OS between different treatments. The median OS was 81 (range 5-156) months, 67 (range 10-153) months, 76 (range 14-146) months, and 78 (range 13-151) months for group I, II, III, and IV, respectively. The significantly lower OS was observed in group II ( P=0.044). Although group II and group III had similar proportion of targeted treatment (43.22% vs 43.24%, respectively), the OS rate was different (67 vs 76 months, P=0.064). Samples from 46 young BC patients were performed on deep sequencing targeting 450 cancer genes. The most common mutations were TP53 (56%), GATA3 (29%), ERBB2 (27%), CDK12 (20%), and FGFR1 (20%). Different from previous studies, only 4.35% (2/46) of BRCA1/2 mutations were detected in this cohort. The mutation frequency of GATA3 in group II was significantly lower than that in group III (0% vs 71.43%, P=0.017). Conclusions: The most common pathological type of young BC was infiltrative duct carcinoma. The OS of HR+/HER2+ patients were significantly lower than that of others. Our results showed that GATA3 could be a potential biomarker for OS prediction for BC with HER2+, which help to further guide targeted therapy in young BC patients.

Metastatic Anal Lesion of Primary Lobular Breast Carcinoma- An Insidious, Rare and Subclinical Progression: Case Report and Review of the Literature

Gastrointestinal metastasis from primary breast carcinoma is very uncommon, with less than 1% of breast carcinomas metastasize to the gastrointestinal tract but anorectal involvement is even rarer. These metastatic lesions can lead to diagnostic challenge for clinicians as they can mimic primary colo-rectal cancer due to the lack of diagnostic signs. The increase of patient survival could lead to an unusual late resumption of metastatic disease, often for a long-time occult. Nowadays, an almost completely absent literature is unable to suggest diagnostic pathways capable of predicting this type of disease evolution. We present the case of a 76-year old woman who underwent treatment for an infiltrative lobular carcinoma of the breast who developed metastasis of the anal canal 11- years later. A literature review was performed.

Detection of Breast Cancer Recurrence by Using Positron Emission Tomography with 18 Fluorodeoxyglucose (FDG-PET)-Computed Tomography (CT) and Tumor Markers

Abstract Background: Breast cancer is responsible for nearly 15% of death in female cancer related death in western countries and is cosidered the second leading cause to death due to cancer in females. In Egypt, it is the most common cancer in female, representing about 38.8% of total cancer cases in women. Early diagnosis of recurrent breast cancer is crucial to selection of the most appropriate therapy. FDG-PET/CT has been used for diagnosis, staging, monitoring response to therapy, and restaging patients with breast cancer. Although FDG-PET/CT may have limited diagnostic value in detecting small primary breast tumors, in staging of the axillary region, and in detecting osteoblastic metastases, it is superior to conventional imaging modalities in detecting distant metastases and in monitoring response to therapy. Aim of Study: To evaluate the role of PET/CT and tumor markers in detection of breast cancer recurrence in Clinical Radio-Diagnosis Department. Patients and Methods: Twenty five female patients their age was from 22-67 years (mean 43 years) all with breast cancer history and elevated serum tumor markers after their initial diagnosis were retrospectively evaluated. PET/CT results were confirmed by further imaging, and follow-up. Changes in further management based on PET/CT were recorded. Results: The patients' age was from 22-67 years. Most of them were (60%) were premenopausal. In this study, 92% had Infiltrating Ductal Carcinoma (IDC) while only 2 patients (8%) had Infiltrating Lobular Carcinoma (ILC), fourteen patients (56%) had recurrence of tumor, and 11 (44%) patients showed no further evidence of disease. Fourteen patients had abnormal PET/CT studies, and 11 patients had normal studies with an overall sensitivity, specificity, and accuracy of 85.7%, 81.8%, and 84%, respectively. PET/CT was compared with contrast-enhanced CT and had a higher sensitivity (85.7% vs. 71.4%), specificity (81.8% vs. 45.4%), and accuracy (84% vs. 60%). PET/CT was also compared with tumor markers and had a higher sensitivity (85.7% vs. 78.5%), specificity (81.8% vs. 18.1%), and accuracy (84% vs. 52%).Conclusion: FDG-PET/CT was superior to conventional imaging modalities in diagnosis of breast cancer recurrence.

Influence of Tumor Subtype, Radiological Sign and Prognostic Factors on Tumor Size Discrepancies Between Digital Breast Tomosynthesis and Final Histology.

BackgroundInfluence of tumor subtype, radiological sign and prognostic factors on tumor size discrepancies between DBT and final histology has not been completely investigated so far.PurposeTo study the influence of tumor subtype, radiological sign and prognostic factors on tumor size discrepancies between digital breast tomosynthesis and final histology.Material and methodsThis is a retrospective study conducted between January 2015 and December 2016. After IRB approval, 130 consecutive patients with breast cancer diagnosed with digital breast tomosynthesis (DBT) were evaluated. A discrepancy between DBT and final histology was considered present if the difference was above the cut-off of 5 mm. Tumor subtype, radiological sign and prognostic factors were evaluated in patients with discrepancies. Descriptive statistic and non-parametric tests were used.ResultsA total of 105 cases of cancer, in 96 patients, all female, were included. Mean age was 61 years (range: 35-82 yrs). In 19 (18.1%) cases, discrepancies were found: 13 (68.4%) were underestimated by DBT. For tumor subtype, 10 (52.6%) were infiltrating lobular carcinomas (ILC) (p < 0.01). Fourteen (73.7%) discordant cases were architectural distortions (p < 0.01). Prognostic factors did not affect tumor size discrepancies.ConclusionILC or an architectural distortion represents the majority of cases of tumor size discrepancies between DBT and final histology.

Abstract P4-02-04: Tumor-infiltrating lymphocytes in invasive lobular breast cancer identify a poor prognostic sub-group

Abstract Background: Tumor infiltrating lymphocytes (TILs) are associated with an improved outcome in triple negative and HER2 breast cancers. Conversely, a recent pioneer study showed that TILs in infiltrating lobular carcinoma (ILC) were associated with a worse prognosis. We aimed at assessing the prognostic impact of TILs in a large cohort of primary surgically treated ILC with a long follow-up in a single institution. Methods: We retrospectively reviewed 459 ILC treated at the Curie Institute between 2005 and 2008. Clinico-pathological patients' characteristics were collected and all archived tumor slides were centrally reviewed for TILs quantification. We analyzed stromal TILs scored as a continuous variable. Cox analyses were performed for relapse free survival (RFS) and for overall survival (OS), and chi-square and Fisher test were performed to evaluate the correlation between TILs and other clinico-pathological variables. For statistical analyses, presence or absence of TILs was considered. Results: Patients had a mean age of 60.3 years and a median follow-up of 8.8 years, during which 74 local and/or distant relapse events occurred, among which 37 deaths due to the disease. The presence of TILs were significantly associated with greater tumor size (pT), positive nodal status (pN), molecular class (HER2 amplified), and specific morphological nuclear features such as high nuclear grade, multinucleation, macronucleoli and high Nottingham Prognostic Index class. Presence of intra-tumoral lymphocytes is significantly associated with a worse RFS (HR: 2.07 p=0.003) and OS (HR: 4.58 p&amp;lt;0.001) in a multivariate analysis, independently of chemotherapy. Relapse Free Survival TILs% (IC 95%)% (IC 95%)No95.3 (92.5-98.2)89.0 (84.3-94.0)Yes89.3 (85.1-93.6)74.0 (67.5-81-1) Overall Survival OS at 5 yearsOS at 10 yearsTILs% (IC 95%)% (IC 95%)No99.5 (97.8-100)95.8 (92.3-99.4)Yes95.3 (92.3-98.1)83.5 (77.8-89.7) Conclusion: TILs are an independent prognostic factor associated with a poor outcome in ILC that are easy to assess on diagnostic biopsies. In order to elucidate the role of TILs in ILC, we will further characterize the immune infiltrate and integrate these results with DNA, RNA and protein analyses of the same carcinomas, in order to gain insight into their molecular features and to facilitate the identification of new therapeutic strategies for these ILC with TILs. Citation Format: Tille J-C, Saint Martin C, Fuhrmann L, De Koning L, Reyal F, Piccart M, Kirova Y, Cottu P, Carton M, Vincent Salomon A. Tumor-infiltrating lymphocytes in invasive lobular breast cancer identify a poor prognostic sub-group [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-02-04.

Increased RNA Expression of von Willebrand Factor Gene Is Associated With Infiltrating Lobular Breast Cancer and Normal PAM50 Subtype.

Infiltrating lobular carcinoma (ILC) is the second most common histologicaI subtype of breast cancer, accounting for 10% of all cases. ILC has a characteristic genomic profile. ILC shows a high frequency of cadherin 1 (CDH1) mutations, along with loss of phosphatase and tensin homolog (PTEN), activation of alpha serine/threonine kinase (AKT), and mutations in T-box transcription factor (TBX3) and forkhead box protein A1 (FOXA1). We suspected that another gene, von Willebrand factor (VWF), might also be part of the profile, since coagulation tests reveal significant differences in patients with breast cancer. For newly-diagnosed breast cancer, the association between VWF and histology in the GDC Breast Cancer dataset in The Cancer Genome Atlas (TCGA) was evaluated. The following were used to access and analyze the data: Genomic Data Commons Data Portal (https://portal.gdc.cancer.gov/); Xena browser (https://xenabrowser.net); cBioportal (http://cbioportal.org); Oncomine (https://oncomine.org); and Prediction Analysis of Microarray 50 (PAM50). Patients with ILC had higher VWF RNA expression than patients with infiltrating ductal carcinoma and other histology. The difference of expression was present to the same degree in both pre-menopausal and post-menopausal patients. Nine alterations in VWF and PTEN were significantly co-occurrent. Considering all histologies in 843 samples, Tukey's honest significant difference post hoc test showed that VWF RNA expression of the normal subtype was significantly greater than that of the other subtypes (p<0.001). Our finding of significantly higher VWF RNA expression in the PAM50 normal (non-basal-like) breast cancer subtype suggests that VWF protein measurement might complement or corroborate PAM50 results. VWF and PAM50 results both suggesting a low risk of recurrence might make the decision whether to give chemotherapy easier, especially if VWF protein were an independent predictor.

Comparison of Two Mindfulness-Based Cognitive Therapies and Acupuncture on the Pain and Depression Index in a Case with Lobular Carcinoma: A Single Case Experimental Study

Introduction: Breast cancer is considered to be the most common diagnosis of cancer in the world. Psychological distresses help to increase the mortality rate in breast cancer and psychotherapy plays an important role in managing syndromes. On the other hand, the effectiveness of acupuncture on psychological indices in patients with breast cancer has a research support. So far, no study has been done to compare the two approaches in patients with breast cancer. Case Presentation: in a single-case experimental design in the form of ABCABC design with multiple baselines with follow-up of 6 months (TCTR20180605001), during January to October 2015, a 37-year-old woman with infiltrating lobular carcinoma (ILC) with metastasis invasion of axillary lymph nodes with dysthymic syndromes, was selected through targeted sampling, and after twenty-one days of evaluation (A1), she was treated for three weeks with auricular acupuncture (B1). After six months, the second phase of the assessment in the form of baseline of second intervention was performed for three weeks (A2) and then three weeks mindfulness-based cognitive therapy (MBCT) (B2) was performed. Phase C1 was performed as follow-up acupuncture and six months after mindfulness cognitive therapy follow-up (C2) was done. Pain index was considered as the primary outcome and depression index as secondary outcome and the results were evaluated through the control of the trend of the multiple baselines through visual analysis. Conclusions: Data analysis showed that acupuncture was associated with a reduction in pain in the patient (P 0.05). Also, the mindfulness significantly reduced the depression and pain index (all < 0.05). However, the effectiveness of these treatments was not maintained during the follow-up phase (all < 0.05). These findings can be useful in convergence of therapeutic models in order to formulate effective interventions strategies and to be considered as a link between psychological and biological approaches.

Anorectal metastasis from breast carcinoma: a case report and review of the literature

BackgroundGastrointestinal metastasis from primary breast carcinoma is uncommon, anorectal involvement is extremely rare.Case presentationWe present the case of a 65-year old woman who underwent treatment for an infiltrative lobular carcinoma of the left breast with bone metastases and who developed metastasis of the rectum and anal canal 4 years later.ConclusionsA patient with a history of breast cancer, especially lobular carcinoma, presenting with anorectal symptoms, should raise the suspicion of metastatic disease.

Role of Immunohistochemistry in Early Detection of Bone Marrow Micrometastases in Breast Cancer

BackgroundIn Egypt, breast cancer (BC) accounted for 37.7% as reported from WHO in 2008. Mammaglobin (MAM) is BC specific marker, which is almost expressed in breast epithelial cells. It is over expressed in subset of 70–80% of primary and metastatic BC tissues and can be used for identification of BC cells in bone marrow (BM).ObjectivesTo evaluate the significance of immunohistochemical (IHC) method applied on bone marrow trephine biopsy (BMB) in increasing the detection capacity for BC micrometastases in apparently non stage‐IV patients. To compare these results with those obtained by cytological examination of BM aspirate and the different biochemical marrow investigations.Materials and MethodsThirty prospective cases, presented with different stages (0‐III) of BC and who received no chemotherapy, were selected from Alexandria Armed Forces Hospital, Egypt, during the period from March 2014 to December 2015. All patient were subjected to the following work up: Reviewing patients' medical records for all clinical and demographic data. BM cytological examination (at least 6–8 Leishman's‐stained BMA smears) was meticulously scanned for any sheets of non‐haemopoietic malignant cells. Histological examination of BM core biopsy (at least 2.5 cm long); minimum of 2 H&amp;E stained sections were thoroughly examined by two histopathologists for any sheets of nonhaemopoietic malignant cells. Morphological interpretation was guided by the standardized morphological criteria. IHC staining was performed on the BMB sections using MAM monoclonal antibody. CA15‐3 serum and BMA plasma levels were assessed using the fully automated Abbott “Axsym” system. Results 22 patients were diagnosed with infiltrating duct carcinoma (IDC) (73.3%), while the rest (26.7%) were diagnosed with infiltrating lobular carcinoma (ILC). Three patients with IDC were classified as grade I (13.6%), 10 as grade II (45.5%), and 9 as grade III (40.9%). Regarding the stage, 2 patients (6.7%) presented with stage 0, 6 patients (20%) with stage I, 14 patients (46.7%) with stage II and 8 patients (26.7%) with stage III (Figure 1). Examination of the BM aspirates of the 30 patients were completely negative (100%), while examination of the H&amp;E stained sections from the BMB were as follows: 5 patients (16.7%) were positive for BM micrometastases showing hypercellularity, fibrosis, inflammatory infiltration (plasma cells, macrophage and eosinophils), angiogenesis and osteoclastic hyperplasia (Figure 2), while 25 patients (83.3%) were negative. 16/30 cases (53.3%) yielded positive results for the MAM IHC staining on BMB (Figures 3 and 4). There was statistical significant differences between using MAM IHC staining and BMB H&amp;E examination (P=0.0013). By measuring CA15.3 in both serum and BM plasma, there was no statistical significant difference regarding serum and BM plasma CA15.3. Conclusions Superiority of BMB over BMA in detection of BM micrometastatic disseminated tumor cells (DTCs) in patients diagnosed with primary BC. Combining BMB with IHC staining using MAM significantly increases the detection capacity for DTCs in the BM when diagnosing patients with primary BC. In spite of the correlation present between BM plasma and serum levels of CA15‐3, neither CA15‐3 serum levels nor BM plasma levels could be reliable markers for diagnosing or detecting early occult micrometastatic DTCs in the BM at initial diagnosis of primary BC This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Invasive lobular carcinoma of the breast: A special histological type compared with invasive ductal carcinoma.

The clinical outcomes and therapeutic strategies for infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) are not uniform. The primary objectives of this study were to identify the differences in the clinical characteristics and prognoses between ILC and IDC, and identify the high-risk population based on the hormone receptor status and metastasis sites. The Surveillance, Epidemiology, and End Results Program database was searched and patients diagnosed with ILC or IDC from 1990 to 2013 were identified. In total,796,335 patients were analyzed, including 85,048 withILC (10.7%) and 711,287 withIDC (89.3%). The ILC group was correlatedwith older age, larger tumor size, later stage, lower grade, metastasis disease(M1) disease, and greater counts ofpositive lymph nodesandestrogen-receptor-positive (ER)/progesterone receptor-positive (PR) positive nodes. The overall survival showed an early advantage for ILC but a worse outcome after 5 years. Regarding the disease-specific survival, the IDC cohort had advantages over the ILC group, both during the early years and long-term. In hormone status and metastasis site subgroup analyses, the ER+/PR+ subgroup had the best survival, while the ER+/PR- subgroup had the worst outcome, especially the ILC cohort. ILC and IDC had different metastasis patterns. The proportion of bone metastasis was higher in the ILC group (91.52%) than that in the IDC (76.04%), and the ILC group was more likely to have multiple metastasis sites. Survival analyses showed patients with ILC had a higher risk of liver metastasis (disease-specific survival[DSS]; P = 0.046), but had a better overall survival than the bone metastasis group (P<0.0001). We concluded that the long-term prognosis for ILC was poorer than that for IDC, and the ER+/PR- subgroup had the worst outcome. Therefore, the metastasis pattern and prognosis must be seriously evaluated, and a combination of endocrine therapy and chemotherapy should be considered.

Invasive lobular breast carcinoma metastasising to the rectum

Gastrointestinal (GI) metastasis from a primary breast carcinoma is uncommon, with the rectum being one of the least reported sites in the literature. We report a case of a 79-year-old...